The yeast HtrA orthologue Ynm3 is a protease with chaperone activity that aids survival under heat stress.
Ynm3 is the only budding yeast protein possessing a combination of serine protease and postsynaptic density 95/disc-large/zona occludens domains, a defining feature of the high temperature requirement A (HtrA) protein family. The bacterial HtrA/DegP is involved in protective stress response to aid survival at higher temperatures. The role of mammalian mitochondrial HtrA2/Omi in protein quality control is unclear, although loss of its protease activity results in susceptibility toward Parkinson's disease, in which mitochondrial dysfunction and impairment of protein folding and degradation are key pathogenetic features. We studied the role of the budding yeast HtrA, Ynm3, with respect to unfolding stresses. Similar to Escherichia coli DegP, we find that Ynm3 is a dual chaperone-protease. Its proteolytic activity is crucial for cell survival at higher temperature. Ynm3 also exhibits strong general chaperone activity, a novel finding for a eukaryotic HtrA member. We propose that the chaperone activity of Ynm3 may be important to improve the efficiency of proteolysis of aberrant proteins by averting the formation of nonproductive toxic aggregates and presenting them in a soluble state to its protease domain. Suppression studies with Deltaynm3 led to the discovery of chaperone activity in a nucleolar peptidyl-prolyl cis-trans isomerase, Fpr3, which could partly relieve the heat sensitivity of Deltaynm3.
Padmanabhan
Nirmala
N
Abteilung Molekulare Mikrobiologie und Genetik, Institut für Mikrobiologie und Genetik, Georg August Universität Göttingen, Germany.
Fichtner
Lars
L
Dickmanns
Achim
A
Ficner
Ralf
R
Schulz
Jörg B
JB
Braus
Gerhard H
GH
D000818:Animals; D002470:Cell Survival; D017353:Gene Deletion; D018869:Heat-Shock Response / Q000502:physiology*; D006358:Hot Temperature; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C511243:NMA111 protein, S cerevisiae; D012697:Serine Endopeptidases